Outcomes following venetoclax-based treatment in therapy-related myeloid neoplasms
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(Published version)
Date
2022
Authors
Shah, M.V.
Chhetri, R.
Dholakia, R.
Kok, C.H.
Gangat, N.
Alkhateeb, H.B.
Al-Kali, A.
Patnaik, M.M.
Baranwal, A.
Greipp, P.T.
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Journal article
Citation
American Journal of Hematology, 2022; 97(8):1013-1022
Statement of Responsibility
Mithun Vinod Shah, Rakchha Chhetri, Ruchita Dholakia, Chung H. Kok, Naseema Gangat, Hassan B. Alkhateeb, Aref Al-Kali, Mrinal M. Patnaik, Anmol Baranwal, Patricia T. Greipp, Rong He, Kebede H. Begna, Ing Soo Tiong, Andrew H. Wei, Devendra Hiwase
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Abstract
Therapy-related myeloid neoplasms (t-MN) are aggressive malignancies in need of effective therapies. The BCL-2 inhibitor venetoclax represents a paradigm shift in the treatment of acute myeloid leukemia. However, the effectiveness of venetoclax has not been studied in a large cohort of t-MN. We retrospectively analyzed 378 t-MN patients, of which 96 (25.4%, 47 therapy-related acute myeloid leukemia, 1 therapy-related chronic myelomonocytic leukemia, 48 therapy-related myelodysplastic syndrome) received venetoclax. Median interval from t-MN to venetoclax initiation was 2.9 (Interquartile range [IQR] 0.7–12) months, and patients received a median of 3 (IQR 1–4) cycles. The composite complete remission (CRc) rate, median progression-free survival (PFS), and overall survival (OS) were 39.1%, 4.9 months, and 7 months, respectively. The upfront use of venetoclax and achieving CRc were associated with improved survival, whereas the presence of Chromosome 7 abnormalities was associated with an inferior survival. Neither the TP53-status nor the percent bone marrow blast predicted the likelihood of CRc or survival. Paired genetic analysis performed at venetoclax initiation and failure did not show the evidence of the selection of the TP53-mutated clone. In a propensity-matched analysis, the use of venetoclax-based regimen as the first-line therapy was associated with a superior survival compared to hypomethylating agent (HMA)-based first-line therapy (9.4 vs. 6.1 months, p = .01). We conclude that the upfront use of venetoclax with HMA improved survival, though PFS and OS remain poor. As the phenotype at diagnosis or the percent blasts did not predict outcomes, venetoclax should be studied in all t-MN phenotypes.
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First published: 12 May 2022
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© 2022 The Authors.American Journal of Hematology published by Wiley Periodicals LLC. This is an open access article under the terms of theCreative Commons Attribution-NonCommercial-NoDerivsLicense, which permits use and distribution in anymedium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.